Vibrational optical activity (VOA), which is comprised of Raman optical activity (ROA) and vibrational circular dichroism (VCD), will be advanced along instrumental, interpretational and theoretical lines with the aim of improving existing methods for the determination of the solution-phase conformations of biomolecules. A multichannel ROA spectrometer will be upgraded by replacing the OMA 2 computer console with an OMA III console and adding the capability of a multichannel charge coupled device (CCD) detector to achieve greater instrumental reliability and spectral sensitivity. New instrumental approaches to the measurement of ROA, recently conceived and devised in our laboratory, and referred to as scattered circular polarization (SCP) ROA and dual circular polarization (DCP) ROA, will be exploited for their enhanced efficiency and stability over conventional ROA measurement techniques, termed incident circular polarization (ICP) ROA. Measurements will focus initially on molecules that have already exhibited strong ROA spectra in solution and will proceed toward similar molecules of greater complexity. Approaches to the measurement of resonance ROA will also be explored. Such measurements are of interest because of their structural selectivity and because theoretical differences between SCP and ICP ROA are predicted to be enhanced under resonance Raman conditions. Applications of VOA to the study of biomolecular conformations will be highlighted by measurements of VCD using any one of three existing VCD spectrometers at Syracuse University. Samples to be measured include amino acids, simple peptides, glyceraldehyde, catecholamine neurotransmitter molecules, tripodal peptides, azidomethemoglobin and azidometmyoglobin, and additional selected proteins, amines, alcohols, sugars and related molecules. The VCD spectra will be interpreted by using or extending the rules of the ring current intensity mechanism or by applying the coupled oscillator intensity mechanism. Particular attention will be devoted to the sensitivity of VCD, via the ring current mechanism, to the presence of intramolecular hydrogen bonds, some of which involve only weak forms of intramolecular association such as oxygen lone pair to aliphatic carbon hydrogen interactions. Vibronic coupling expressions of VCD and ROA intensities and comparison to experimental results. Emphasis will be placed on relating the results of calculations to elementary VOA models and interpretational approaches, such as the ring current mechanism of VCD. Model diols and amino alcohols, alanine and deuteriated glycine will serve as initial targets for calculations. As in previous years, the primary focus of this research will be on amino acids and peptide molecules; however, research on other types of molecules that are well suited to the goals of this program will be pursued as part of a more flexible approach to VOA research.